Engineered proteins are revolutionizing immunotherapy, but advances are still needed to harness their full potential. Traditional protein engineering methods use naturally existing proteins as a starting point, and therefore, are intrinsically limited to small alterations of a protein's natural structure and function. Conversely, computational de novo protein design is free of such limitation, and can produce a virtually infinite number of novel protein sequences, folds, and functions. Recently, we used de novo protein engineering to create Neoleukin-2/15 (Neo-2/15), a protein mimetic of the function of both interleukin-2 (IL-2) and interleukin-15 (IL-15). To our knowledge, Neo-2/15 is the first de novo protein with immunotherapeutic activity, and in murine cancer models, it has demonstrated enhanced therapeutic potency and reduced toxicity compared to IL-2. De novo protein design is already showcasing its tremendous potential for driving the next wave of protein-based therapeutics that are explicitly engineered to treat disease.

中文翻译：

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从头蛋白的出现用于癌症免疫治疗。

工程蛋白正在彻底改变免疫疗法，但仍需要进一步发展以发挥其全部潜力。传统的蛋白质工程方法以天然存在的蛋白质为起点，因此，本质上仅限于蛋白质天然结构和功能的微小改变。相反，从头计算蛋白质的设计不受这种限制，并且可以产生几乎无限数量的新颖蛋白质序列，折叠和功能。最近，我们使用从头蛋白质工程来创建Neoleukin-2 / 15（Neo-2 / 15），这是一种白介素2（IL-2）和白介素15（IL-15）的功能模拟蛋白。据我们所知，Neo-2 / 15是第一个具有免疫治疗活性的从头蛋白，在鼠癌模型中，与IL-2相比，它具有增强的治疗功效和降低的毒性。从头蛋白质设计已经显示出其巨大潜力，可以推动下一波基于蛋白质的疗法的发展，这种疗法被明确设计用于治疗疾病。